Study of V(1)-vascular vasopressin receptor gene microsatellite polymorphisms in human essential hypertension

• Published in: Journal of molecular and cellular cardiology Vol. 32; no. 4; pp. 557 - 564
• Main Authors: Thibonnier, M, Graves, M K, Wagner, M S, Chatelain, N, Soubrier, F, Corvol, P, Willard, H F, Jeunemaitre, X
• Format: Journal Article
• Language: English
• Published: England 01-04-2000
• Subjects: Alleles; Base Sequence; DNA, Complementary; Gene Frequency; Genetic Linkage; Humans; Hypertension - genetics; Introns; Microsatellite Repeats; Molecular Sequence Data; Polymorphism, Genetic; Receptors, Vasopressin - genetics
• ISSN: 0022-2828

Vasopressin (AVP) actions on vascular tone and blood pressure are mainly mediated by the V(1)-vascular receptor (V(1)R). We recently reported the structure and functional expression of the human V(1)R cDNA and described the genomic characteristics, tissue expression, chromosomal localization, and regional mapping of the human V(1)R gene, AVPR1A. To test whether the V(1)R is a marker for human essential hypertension, we sequenced the human AVPR1A gene and its 5; upstream region and found several DNA microsatellite motifs. One (GT)(14)-(GA)(13)-(A)(8)microsatellite is located 2983 bp downstream of the transcription start site, within a 2.2 kbp intron interrupting the coding sequence of the receptor. Three other microsatellites are present in the 5; flanking DNA of the AVPR1A gene: a (GT)(25)dinucleotide repeat, a complex (CT)(4)-TT-(CT)(8)-(GT)(24)motif and a (GATA)(14)tetranucleotide repeat located respectively 3956 bp, 3625 bp and 553 bp upstream of the transcription start site. Analysis of these polymorphisms in 79 hypertensive and 86 normotensive subjects for the (GT)(14)-(GA)(13)-(A)(8)and the (GT)(25)motifs revealed a high percentage of heterozygosity but no difference in alleles frequencies between the two groups. A linkage study using the affected sib pair method and the (GT)(25)repeat in 446 hypertensive sib pairs from 282 French Caucasian pedigrees showed no excess of alleles sharing at the AVPR1A locus. No linkage was found in the subgroups of patients with early onset hypertension (diagnosis before age 40) or severe hypertension (diastolic blood pressure >/=100 mmHg or requirement for >/=two medications). These findings suggest that molecular variants of the V(1)R gene are not involved in unselected forms of essential hypertension.